EP2907535B1

EP2907535B1 - Syringe type pump

Info

Publication number: EP2907535B1
Application number: EP15154808.8A
Authority: EP
Inventors: Paul HADVÁRY; Hansjörg Tschirky
Original assignee: Pharmasens AG
Current assignee: Pharmasens AG
Priority date: 2010-10-11
Filing date: 2011-10-07
Publication date: 2024-02-07
Anticipated expiration: 2031-10-07
Also published as: ES2970794T3; EP2907535A3; US20130324884A1; CA2813525A1; CN103313741A; JP2015231560A; US20150273139A1; JP6490534B2; EP2627374A2; US10130756B2; CA2895617A1; CN105126194B; CN105126194A; CA2895617C; JP6434454B2; CN103313741B; JP2016190058A; EP2907535C0; DK2627374T3; JP2017148596A

Description

The present invention is related with a device for subcutaneous injection according to the preamble of claim 1.
One major field of application for this type of device is the injection of physiologically active fluid into a patient and/or the extraction of body fluid for diagnostic purposes. For this use the devices are usually equipped with both a contact surface for attaching to a patient's skin and a cannula for the access to the patient's tissue or vessels for introducing an injection fluid or the removal of analysis fluid.
Injection devices are widely used in patient care but their size and complexity largely restricts their use to specialized facilities. Recently, ambulatory use of injection devices has been pioneered in diabetes care for the delivery of insulin.
More recently, because of these drawbacks, infusion devices which can be attached directly to the skin, preferably without long barrels connecting to the subcutaneous delivery cannula are being developed. Due to the necessary reduction in size and weight the precise syringe-type pumps with sufficient volume of injection fluid are difficult to use attached directly to the skin. Therefore, alternative pump types with considerable drawbacks in precision and reliability of delivery under the highly variable environmental and physiologic conditions encountered during real-life operation have been incorporated, e.g. delivery from a reservoir with peristaltic pumps, with piston pumps using valves, or by squeezing a flexible container.
Wearable drug delivery devices with needles or cannulas and base or bottom members provided with adhesive layers for attachment to a patient's skin are known. For protection of the cannulas prior to and after use the base members are shaped such that they project beyond the cannula tips. For drug delivery the devices are attached to patients and the cannulas are inserted into the skin.
Document US 5,931,814 discloses a dermally affixed injection device with a base plate in the form of a cup spring which is provided with an annular adhesive layer for attachment to a patient. Prior to use the base plate is bent to a prestressed shape in which it projects beyond the cannula tip for protecting the cannula. When the spring is released it snaps into its flat position to allow the skin to move towards the cannula.
US 2004/0116865 discloses a wearable drug infusion device with a base plate provided with an adhesive layer. The base plate has the form of a bistable disc member having a convex and a concave shape. Prior to use the disc member is in its convex shape to protect the needle. To attach the device to a patient and insert the needle the device is manually pressed onto the skin, thereby causing the bistable disc to snap to its concave shape and the needle to be pressed into the skin.
US 2002/0022798 discloses a wearable drug infusion device with a collapsible bottom cover which prior to use projects beyond the height of the needle. For insertion of the needle into a patient's skin the device is manually pressed onto the skin so that the bottom cover collapses and the needle is pressed into the skin.
2. Syringe pumps for such applications have barrels with a wide diameter in order to avoid an extended longitudinal footprint, but this solution has disadvantages necessitating high driving forces to inject against a considerable tissue back-pressure and most importantly because of the risk of air bubbles entering and occluding the injection cannula due to almost unavoidable relatively large dead-volumes, and unintended, relatively large bolus injections due to stick-slip effects.
In this context is known from US 5,931,814 a dermally affixed injection device with a cannula which prior to use is protected by a base plate being in a prestessed position and after release taking a flat position to allow the skin to move against the cannula. This device, however, cannot be used for patients having a skin with low elasticity.
Several solutions have been suggested for actively pulling the skin towards the cannula. US 2004/0116865 discloses a needle insertion device with a rigid base plate which is adhesively attached to the skin and has a central portion which upon pressure onto the casing snaps inwards and pulls a small region of the skin towards the needle. US 2002/022798 discloses a fluid delivery device with a needle which is pressed into the skin by turning a selector knob. US 6,186,982 discloses a drug delivery device in which by pressing the casing with a needle towards a hinged base plate whereby the needle pierces the skin. US 4,393,870 discloses an injection device with which the patient's skin is sucked against a cannula by use of a vacuum. None of the disclosed insertion mechanisms fulfills all the desired requirements, such as painless skin piercing, compatibility with patch-type devices or reliability of skin piercing.
The aim of the present invention is to provide an injection device with an improved insertion method which avoids the disadvantages of the state of the art devices.
According to the invention this is achieved by the characterising features of claim 1.
The device has a contact surface for contacting a patient's skin or an intravenous port. Typically, the contact surface to the skin is coated with an adhesive and the syringe pump is linked to a cannula having a tip which is configured and dimensioned for piercing the patient's skin or a septum of a port and introducing an injection fluid into the patient or removing analysis fluid.
In preferred embodiments, the inventive device has a cannula which is fixedly positioned relative to a casing and to the syringe pump. The insertion mechanism of the cannula into the patient's skin comprises preferably a flexible contact surface adhering to the skin.
When used herein, the following definitions define the stated term
Adhesive contact surface for temporary wearing on the skin is made of materials with strong adhesive properties, stretchability and minimal allergenicity. This adhesive layer is fixed on the base of the device either covering the entire surface or at least its central part leaving a free rim in such a way that it does not interfere with its flexibility. Preferentially the surface of the adhesive layer which is fixed to the skin is significantly larger than its surface which is fixed to the flexible base of the device, leaving a rim which is not fixed to the flexible base. This can be accomplished e.g. by an adhesive layer extending beyond the surface of the base of the device or, preferentially by using a shape for the adhesive surface to the skin similar to or only slightly larger than the surface of the flexible surface of the device but fixing it to the latter in such a way that an outer annular zone is not fixed to the base of the device. Such a design is described in EP0825882 for a medical device with a rigid base.
Analysis fluid is blood, interstitial fluid or dialysate having been in contact with interstitial fluid through a semi-permeable membrane.
Analyte means any endogenous or exogenous substance the concentration of which can be used to diagnose the health, organ function, metabolic status, or drug metabolizing capacity of an individual. Examples of endogenous substances are glucose, lactate, oxygen, creatinine, etc. Examples of exogenous substances are drugs, metabolites of such drugs, diagnostic substances (e.g. inulin) etc.
Component with a flexible surface is made up of a casing which has preferentially a circular or oval footprint and which has a flexible base. This base plate is constructed in such a way that it can be deformed to a convex shape with a protruding part e.g. like a cone or a gable (position 1). An additional feature of this base is that it can shoot from the convex shape into a flat shape (position 2) with sufficient velocity and force that this movement can provide the driving energy for implantation of the implantable parts of injection cannulas or diagnostic probes by pulling the skin attached by the adhesive surface against the tip of the cannulas or diagnostic probes. Such a flexible surface can be achieved by appropriate segmentation of the surface with hinge regions acting as springs and/or by using elastic materials with the necessary reversible stretching characteristics which moves e.g. from a pre-stressed shape to adopt a flat, relaxed shape.
Means to position the flexible surface relative to the the implantable parts of injection cannulas or diagnostic probes in two defined positions consists of elements which can bring about the deformation of the flexible surface to a convex, pre-stressed shape and allow a rapid release from this position to adopt a flat, relaxed shape in a coordinated way for the entire surface. This can be accomplished preferentially by several pin-shaped elements protruding from the flexible surface and pushing onto a sliding bolt mechanism, but other constructions using screws, ramps, levers etc. are also possible.
Such a component with a flexible surface can be manufactured by injection molding of suitable plastics but also by using other materials like steel, composite or ceramic materials, etc. The base of this element has an opening in form of a hole or slit, as opening for the implantable parts of injection cannulas or diagnostic probes. The implantable parts of injection cannulas or diagnostic probes are positioned axially to this base in such a way that in position 1 they are entirely covered up, whereas in position 2 they protrude the base.
Delivery of injection fluid encompasses both relatively fast injection (bolus) and relatively slow introduction (also called infusion or instillation) of a liquid into the body.
Diagnostic probe is the functional element for the determination of analyte concentrations and means, but is not restricted to, any analysis fluid removal and on-line analysis or sampling system. In case of a micro-dialysis system a dialysis membrane forms the interface between the interstitial fluid and a dialysis fluid which is passed at the other side of the membrane. In a preferred embodiment a micro-dialysis probe consists of an outer and an inner barrel, covered at the implantable tip by a dialysis membrane. The inner barrel is connected to the pump which delivers the dialysis fluid and the outer barrel is connected to an analysis or sampling system.
Functional package is designed to hold the rigid part of the device by a releasable coupling mechanism and has a removable cap to protect the active surface of the diagnostic probes during storage in a defined environment, such as humidity and allows maintaining sterility. The functional package has also a rim element allowing, after removal of the cap, the correct attachment of the rim of the adhesive layer by pressing against the skin. Further, the functional package protects the release/start mechanism of the device against premature, unintended operation and the release/start mechanism can be actuated only following attachment of the device to the skin and removal of the functional package.
Intravenous port comprises a catheter placed into a vein and having a connective element, preferably a septum at the exterior end of the catheter.
Sampling means is the functional element for collecting samples of analysis fluid for determination of analytes external to the device by, but not limited to biochemical, immunological, HPLC, or LC/MS/MS methods. The samples can be collected in separated receptacles or in a continuous cavity, e.g. a barrel or tube taking precautions that mixing of samples taken at different times is reduced to a minimum. This can be achieved e.g. by introduction of segments of air or of a non-miscible fluid into the analysis fluid creating separated samples in the continuous cavity.
Sliding bolt mechanisms adapts upon a circular or linear movement consecutively several fixed positions and consists of elements which display a closed or open state, for example a solid surface or a hole. The movement of the slide mechanism is driven manually or for example by a spring actuated by a release element, for example through pressing or releasing a button or handle, or through a turning movement. For inserting in parallel a fluid delivery cannula and a flexible sensor within a guide needle into the skin by means of a component with a flexible surface attached to the skin, movement of the sliding bolt mechanism from the storage position (position 1) to the next position (position 2) upon an easy manipulation actuates a rapid release of the flexible surface from a pre-stressed shape to adopt a flat, relaxed shape and inserts the fluid delivery cannula and the sensor guide needle into the skin. The interim blockage of the sliding bolt mechanism at position 2 is now released and allows to actuate the movement of the sliding bolt mechanism to the next position (position 3), which actuates the partial retraction of the guide needle.
In the following preferred embodiments of the invention are described with reference to the accompanying drawings in which

Fig. 1: is a diagrammatic sectional top view of an injection device with a circular syringe pump showing the principle of a circular syringe pump according to state of the art construction but with an improved solution allowing a limited adaptation of the piston to the curvature of the barrel.
Fig. 2: is a diagrammatic cross sectional view of a syringe filling and an injection cannula insertion mechanism into the skin according to one embodiment of the invention.

The injection device shown in Fig. 1 has a casing having a cylindrical side-wall 1 housing a barrel in form of a segment of a toroidal tube 2. One end 3 of the barrel is provided with a connecting channel to a cannula (not shown). The barrel has a circular cross section.
A piston 4 is arranged in the interior of the barrel and is provided with a seal fitting tightly at the inner wall of the barrel. The piston is connected to a driving rod 6 which is circularly shaped for driving the piston through the entire length of the barrel.
Using established technologies for manufacturing of a toroidal cylinder the fit between its curvature and the driving rod of the piston will not be perfect. To correct for this the mechanism 5 disclosed here connecting the piston to the rod 6 allowing radial adaptation of the piston represents an improvement as compared to the state of the art solutions e.g. as described by M.P. Loeb and A.M. Olson in US patent 4,525,164 , using a resilient spherical piston which is slidably contacted by a cupped distal end of a driving stem allowing it to rotate within the barrel, since such a construction has intrinsic problems of sealing and friction.
At its end opposite the piston the driving rod has a perpendicularly bent arm 7 extending to a central pivot, thereby reducing the radial component of the force and the resulting friction by moving the piston through the barrel. The inner side of the rod has a gear rim 8 which is driven by a gear drive 9. The gear drive is driven e.g. by a gear train and an electrical motor (for example a watchwork drive) which can be regulated for controlled delivery by signals from inbuilt and/or remote control elements (not shown in the figure). Alternatively, other drives, as known in prior art, can be employed.
Using standard manufacturing technologies for the toroidal barrel such as e.g. plastics-technologies with an injection molding tool having a mandrel which has to be removed by a rotary motion, deviations from a perfect circular shape and variations in its shape are unavoidable due to inherent differences in shrinkage e.g. of the proximal and distal part of the torus wall during manufacturing. Because of this almost unavoidable deviation from an ideal circular shape for the manufactured torus the exact geometric fit between the barrel and the driving rod of the piston moved by a rotary motion can not be secured. Even if the driving rod of the piston is manufactured using steel-technologies with a high level of form-stability, the fit of the attached piston to the barrel's shape along its longitudinal axis becomes variable. Indeed, e.g. a difference of only 2% between the radius of the barrel and of the driving rod causes a serious relative shift which can lead to collision between barrel wall and driving rod for torus arcs of e.g. 150° - 160° which can be manufactured with standard technologies and are aimed at in order to sufficiently reduce the footprint of the syringe-type pump. In addition, the plastics parts usually used to manufacture the housing holding the barrel and the guideways for the driving rod are not absolutely rigid and can slightly deform especially under the applied forces necessary to provide the pressures of several bar to overcome tissue resistance. The resulting radial and axial forces to correct for the actual shape differences between axis of barrel and driving rod can become very substantial with a rigid driving rod which is used for arcuate piston-drive mechanisms described so far. These forces have to be absorbed by the sealing of the piston leading to its deformation causing high friction with resulting stick-slip phenomena up to blockage and/or problems with tightness of the piston. Even if the piston can adapt slightly to correct for the deviation between the axis of the barrel and of the driving rod as described in prior art and with the improvement discussed and exemplified in Fig. 1 the worst case scenario of blockage by clamping between the rigid driving rod and the barrel wall cannot be excluded. Therefore, for medical use of controlled and precise fluid delivery constructions according to prior art in which a driving mechanism with a rigid driving rod is used to move the piston in an arcuate barrel are not sufficiently safe. These problems get even more pronounced at low barrel diameters required for syringe-type pumps intended for the precise delivery of small volumes such as e.g. insulin for diabetic patients.
According to the subject invention, the solution to avoid stick-slip phenomena and/or problems with tightness or even blockage of the piston or clamping between the rigid driving rod and the barrel wall is to use a driving rod of the piston which adapts to the actual curvature of the barrel, being guided and supported by the inner wall of the barrel. In contrast to constructions described in prior art the rod guided and supported by the inner wall of the barrel of the subject invention can adapt to all deviations from the ideal shape and geometry which are unavoidable using cost-effective manufacturing technologies and materials. A preferred embodiment of the subject invention, which can be adapted for both, fluid delivery and fluid withdrawal, is exemplified in Fig 2.
Fig. 2 is the central part of a tangential cut of the device through the end portion 3 of the barrel. A first channel 15 is leading to the upper side of the device and is closed by a septum 14. For filling the barrel with injection fluid a syringe (not shown) having a needle 13 is pierced through the septum 14. Before filling, the piston is touching the end portion 3 of the barrel (not shown). The injection fluid is introduced through channel 15, thereby pushing the piston towards the opposite end of the barrel.
A second channel 17 is leading from the interior of barrel 2 to an injection cannula 16 for delivery of injection fluid into the skin. The cannula 16 is closed at the other end with a septum-seal 18 which is held in a housing 19. The overall construction is such that the dead volume is minimal and no significant volume of air is in the system after filling with injection fluid.
In the exemplified embodiment the insertion means into the skin of the cannula 16 has a flexible base plate 20 which is attached to the skin by an adhesive layer 21. In the ready-to-use mode shown in the figure this flexible base plate is deformed to a convex shape covering the cannula 16. The base plate is preferentially annular or oval and in order to insert a cannula which is remote from the center of the device consists preferentially of two segments with a diagonal slit, forming a gable upon bending. This configuration allows also to use this insertion means for more than one cannula simultaneously which are positioned along the diagonal slit, e.g. if more than one infusion pumps for more than one infusion fluid is used and/or for the combination with insertion of a diagnostic probe into the skin.
By the spring-type mechanism, in addition the septum-seal 18 is pierced by the cannula before it enters the skin. The segments are attached to the circumference of the casing 1 by springy hinge regions and are in addition preferentially made of a flexible material. Alternative forms like a radial segmentation, preferably into 5 to 8 segments with a spacing between them and a central opening, forming a cone upon central bending are also possible if the cannula is placed close to the center of the device.
On its underside, the flexible base plate has an annular or oval adhesive layer for securing the device to the patient's skin with a diagonal slit or a concentric central opening, respectively similar to the base plate. This adhesive layer is composed of three parts, a glue for fixing to the flexible base plate, a textile providing the necessary flexibility and a glue for fixing onto the skin. Suitable materials with low allergenicity potential are commercially available. The adhesive layer can have a larger circumference than the device but it could have also the same circumference if the attachment to the base plate leaves an outer zone where it is not connected to the housing.
Upon release of the pre-stressed base plate actuated e.g. by a sliding bolt mechanism (not shown) it rapidly relaxes to a flat shape towards the bottom of the housing of the device 1, pushes the housing 19 of the septum-seal 18, and the cannula 16 pierces through the septum-seal 18 and through the skin attached by the adhesive layer.
Upon reading this specification, various alternative embodiments will become obvious to the skilled artisan. For example, the drive means for moving the piston or the implantation mechanism of the cannula for delivery of injection fluid into a patient, or for removal of analysis fluid of a patient could be achieved via numerous chemical, mechanical, or electrical means. Further, a large variety of diagnostic elements for the online analysis or for sampling of analysis fluid for removed analysis as well as control and measuring means can be accommodated with the device.
The major advantages of a device with a toroidal syringe-type pump described above are its reduced footprint-size by which it can be comfortably worn and operated by the patient and at the same time the inherent high precision of a syringe type pump. The intrinsic problems of such pumps exemplified in prior art of sealing, friction causing stick-slip phenomena, and even blockage caused by lack of exact fit between the actual form of the arcuate barrel and of the plunger unavoidable in manufacturing of the toroidal barrel and the device using standard cost-effective technologies are solved by using as the drive for the piston a driving rod which is guided and supported by the inner wall of the barrel and therefore can adapt to all deviations from the ideal shape and in geometry. A further advantage is the absence of the problems with connecting tubings between a syringe pump and the cannula penetrating the skin. In addition, the device according to the invention has almost no dead volume thus avoiding complicated mechanisms to move air out of the system during filling of the pump with injection fluid.

Claims

Device for subcutaneous injection of fluid into a patient's skin comprising
- a casing which houses

- a pump (2,4),

- a cannula (16) having a tip for being inserted into the patient's skin, the cannula being fixedly positioned relative to the pump,

- means for inserting the cannula into the patient's skin,

- a flexible base plate (20) being fixed to the casing and having a prestressed convex position in which the tip of the cannula is concealed and a released flat position in which the tip of the cannula is exposed beyond the base plate,

- a mechanism comprising means for holding the base plate in the prestressed convex position and for releasing the base plate to move from its prestressed position to its released flat position,

- characterized by

- an adhesive layer (21) fixed to the flexible base plate and covering at least the central part of the base plate for adhering the base plate onto the patient's skin, whereby when moving from the prestressed convex position to the released flat position the base plate is pulling the adhered skin against the tip of the cannula.
Device according to claim 1, characterized in that the means for bringing the flexible base plate from a first to a second position makes use of the elasticity of this base plate for a rapid movement by relaxation from an enforced tense position.
Device according to claim 1, characterized in that the means for bringing the flexible base plate into two distinct positions comprises a sliding bolt mechanism actuated by pressing a knob.